Apes Incorporated

ApesInc Tests Oral Ebola Vaccine on Chimpanzees

Transfixed by the Ebola deaths of more than 10,000 people in West Africa, the world is largely oblivious to the fact that Ebola is a much larger threat to our endangered cousins, gorillas and chimpanzees. Although vaccines developed for human use would likely protect gorillas and chimps from Ebola, delivering an injectable vaccine to large numbers of wild apes is not feasible. Apes Incorporated is now leading the first-ever chimpanzee trials on an oral Ebola vaccine that could be used to protect entire populations of wild apes.

The trial tests a vaccine combining a snippet of the Ebola coat protein (glycoprotein) with an attenuated form of rabies virus. Chimpanzees will not be challenged with Ebola during the trial. Rather, the trial will establish whether oral delivery of the vaccine is safe and produces a robust immune response similar to that seen in monkeys who were injected with the vaccine then survived Ebola challenge in previous trials by the vaccine’s developer, Professor Matthias Schnell of Thomas Jefferson University. Six chimpanzees at the University of Louisiana Lafayette’s New Iberia Research Center (NIRC) have already been vaccinated orally, with four additional chimps vaccinated through intramuscular injection. Results from the trial are expected in October.

Filoviruses such as Ebola were first recognized as a threat to wild apes in 1994, when a veterinary student conducting a chimpanzee necropsy nearly died when infected with what is now referred to as Ivory Coast virus. Large die-offs of chimpanzees and, particularly, gorillas from Ebola virus (previously Ebola Zaire) then followed in Central Africa during the late 1990’s and 2000’s. Survey data suggest these outbreaks killed about one third of the world gorilla population, leading the International Union for the Conservation of Nature to upgrade the western gorilla species to Critically Endangered on its Red List of Threatened Species. More recently, human filovirus outbreaks have occurred within tens of kilometers of important chimpanzee populations in Guinea and Uganda and the largest remaining population of bonobos in Democratic Republic of Congo. Unfortunately, wildlife management capacity in most of the affected areas is so low that we have no data on wild ape population impact.

The current trial is part of an ongoing Apes Incorporated vaccine program which has included the trial of an injectable Ebola vaccine on chimps at NIRC, a darted measles vaccine trial on wild gorillas in Central African Republic, development of non-invasive methods for assaying vaccine safety and immunogenicity, and field testing of oral baits. “Should oral delivery prove safe and immunogenic in these captive chimps, the next step will be to orally vaccinate wild gorillas at the Ngaga site in Republic of Congo”, said Ape Incorporated President Peter Walsh, also a Lecturer at the University of Cambridge. “This will be the first oral vaccine trial on any wild primate.” Walsh added that the long term objective is not just to protect against Ebola but to develop oral vaccination and non-invasive safety and immunogenicity diagnostics as cost-effective tools for protecting against the many other diseases that increasingly threaten the survival of apes and other wildlife.

The distribution of vaccine-laced oral baits has virtually eradicated fox rabies from Western Europe. However, the wildlife conservation community has been slow to embrace oral vaccination because of safety concerns. A very small amount of orally delivered vaccine passes across the mucosal barrier into the blood stream. Therefore, oral vaccines typically use live viruses that replicate within the host to invoke a robust immune response. The fear that viral replication would produce pathogenic effects has blocked the use of oral vaccination in wildlife.

Schnell’s “filorab1” vaccine was chosen for the chimpanzee trial precisely because of the high safety level of the rabies vaccine on which it is based. The rabies vaccine has been serially passaged and genetically engineered to reduce virulence, tested extensively on captive animals, then distributed in millions of baits across Europe: all with an excellent safety record. “I developed the live attenuated form of the filorab1 vaccine specifically with wild apes in mind”, said Schnell. “The parent rabies vaccine’s outstanding performance in Europe gives us strong reason to believe that the offspring filorab1 vaccine will be equally safe and effective in Africa.”

Not only is Schnell supplying vaccine and diagnostic tests for the chimpanzee trial, NIRC has donated all the animal housing, personnel, and analysis costs for conducting the trial. “This kind of applied research falls in a funding dead zone,” said Walsh. “Basic research funders such as NIH or NSF see it at as too applied while conservation donors see it as not applied enough. We operate on a shoestring, relying on the generosity of people like Matthias and NIRC to get things done.”

Apes Incorporated

First Conservation Vaccine Trial on Chimpanzees

Captive chimpanzees have for the first time been used to test a vaccine to protect wild chimpanzees rather than humans. Published in Proceedings of the National Academy of Science, a new paper shows that a vaccine against the deadly Ebola virus caused no serious side effects and evoked a robust immune response.

Infectious diseases like Ebola have recently emerged as a major threat to wild chimpanzees and gorillas but a viscerally non-interventionist ape conservation community has opposed invasive responses that upset a perceived “natural balance”. “This is not the Garden of Eden”, said Apes Incorporated (ApesInc.org) President and University of Cambridge Lecturer Peter Walsh, senior author on the paper. “It is the Wild West, awash in commercial bushmeat hunting, mechanized logging, and human disease. ‘Extreme Conservation’ measures such as vaccination hold the only hope for preventing ape extinction”.

The trial illustrates the conservation potential held by “orphan” vaccines which show excellent safety and immunity profiles in captive primate trials but have not yet gained the extensive funding needed for human licensing. Chimpanzees were vaccinated with a “virus like particle” vaccine developed by Maryland biotech firm Integrated Biotherapeutics (IBT). “VLP vaccines are particularly promising for use in endangered species because they cannot cause infection and spread between animals”, said IBT Vice President Kelly Warfield. The trial was supported by the Paul G. Allen Family Foundation and included contributions from researchers at the US Army Medical Research for Infectious Disease, the National Institutes of Health, and the University of Louisiana at Lafayette’s New Iberia Research Center, where the trial was conducted.

This promise of vaccination may never be realized because pending regulations to classify captive chimpanzees under the US Endangered Species Act would outlaw further biomedical research on chimpanzees. The closure of facilities doing human-focused biomedical research on chimpanzees is a conservation catastrophe, according to Walsh, because it will leave no place to do the rigorous safety testing that park managers insist on before vaccines are given to immunologically vulnerable wild apes. The US is the only developed country where such testing is still allowed.

The move by the US Fish and Wildlife Service to list captive chimpanzees under the Endangered Species act is only the latest in a series of US Government actions spurred by animal rights activists seeking to end biomedical testing on chimpanzees. There has also been a National Academies of Science blue ribbon panel and an internal policy review by the National Institutes of Health. Although the National Academy panel was specifically mandated by Congress to consider the conservation implications of ending biomedical testing on chimpanzees, neither the Academy’s report, the NIH policy review, nor the regulations proposed by USFWS addressed this important topic.

Vaccination is an important ape conservation issue because over recent decades Ebola virus has killed about one third of the world gorilla population and large numbers of chimpanzees, contributing to the World Conservation Union’s (IUCN) decision to list common chimpanzees as Endangered and western gorillas as Critically Endangered. Human respiratory virus spillover also accounts for about half of deaths among wild chimpanzees and gorillas habituated to close human approach for tourism and research. Most of these viral diseases are preventable: either with vaccines already licensed for human use or with orphan vaccines.

Walsh and coauthors argue that because many of the researchers and tourists that infect wild apes are Americans and because countless wild chimpanzees were killed to originally stock US biomedical labs, the US Government and, particularly, NIH should shoulder the responsibility for alleviating the threat to the wild apes. They call for NIH to establish and support a captive chimpanzee population dedicated solely to conservation research. This population would be used to both safety test conservation vaccines and develop associated technologies such as baiting systems for delivering vaccines orally and non-invasive assays for confirming the immune response to vaccination, measuring whether the psychological stress caused by tourism and research suppress gorilla and chimpanzee immune function, and screening tourists for dangerous respiratory viruses.

Apes Incorporated has an active research program on these and other applications but finds it difficult to raise funds because of the controversial nature of such research: government funding bodies are particularly averse to negative publicity. “The willingness of the Paul G. Allen Family Foundation to fund this work despite the controversy is a perfect example of the critical role that private foundations have to play in preventing ape extinction”, said Walsh. “They understand that not all critical conservation actions will be by consensus. We need to break some eggs to make the conservation omelet. To paraphrase the AIDS prevention movement, Porridge = Death”.

Apes Incorporated

Attaches Radio Telemetry Anklet to Gorilla

IronMan

Apes Incorporated and the Aspinall Foundation are the first to successfully attach a radio telemetry transmitter to an adult male gorilla, a young silverback named Kush at the Port Lympne Wild Animal Park in Kent, UK. To protect against Kush’s formidable canine teeth, the transmitter was embedded in a heavy duty aluminium housing attached to his ankle using a stainless steel chain: codename.

Many people will not like the fact that we used a chain to attach the transmitter or even that we tried to attach anything at all. However, the fact is that western gorillas are now being hunted to extinction. By making western gorilla tourism both economically viable and biologically sustainable, radio telemetry could turn the tide.

Tourism has been very successful in protecting the mountain gorillas of East Africa. However, it has thus far failed to protect the much more numerous but rapidly declining western gorilla. Tourism has not been successful in large part because western gorillas walk about ten times further each day than mountain gorillas. Consequently, habituating them for tourism takes about five years instead of one year. The constant presence of trackers also exposes the gorillas to immunosuppressive stress and human respiratory viruses that cause about half of deaths in habituated gorillas and chimpanzees.

Three years ago we realized that radio tracking could radically accelerate the habituation process, driving down startup time and operating costs by as much as 80%. By drastically reducing the amount of time humans spend with gorillas, telemetry would also minimize stress and human disease spillover. Radio tracking has not been previously used on gorillas both because of anti-interventionist sentiments in the ape conservation community and because of the technical difficulties of attaching radio telemetry devices to gorillas.

How do you attach a radio transmitter to an incredibly powerful animal with effectively no neck and two inch canine teeth? The first step is to find a partner like the Aspinall Foundation, which both cares for gorillas at two parks in England and operates the world’s only successful gorilla reintroduction program in Gabon and Republic of Congo. Two decades in the African conservation trenches have given Aspinall the wisdom to understand that although testing on captive animals is not without risk, these risks are small compared to the potentially huge conservation benefits for animals in the wild. In particular, Aspinall want to use telemetry to rescue reintroduced gorillas who have wandered into areas where they are at high risk of being shot.

In our first try, we wanted to confirm that the classic “collar around the neck” would not work. We bought a collar from a commercial radio telemetry provider and tried to put on the neck of a young silverback at Port Lympne named Timibou. However, his sagittal crest, the muscles on the back of his head and neck, were so big that it just slid right over his head.

Failure!

Our next effort was a belt around Timbou’s waist. Male gorillas have massive chests but tiny, ballerina waists. The belt just slid right down his bum like a pair of gangsta droopy drawers.

Strike two!

Mach 3 was an anklet using the same materials as the collar and waist belt. Timbou immediately smashed the high impact plastic housing protecting the electronics but the heavy duty plastic belting held.

Progress!

Some experienced ape conservationists had warned us that gorillas would injure themselves trying to get an anklet off. But after a day or two of gnawing at the anklet, Timbou completely ignored it.

More Progress!

We’re really moving now, we thought. So we commissioned a new version of the anklet with an aluminium housing covering the electronics. After six weeks we removed the original anklet and replaced it with the armoured one. A close examination of Timbou’s ankle showed that the anklet had not caused any injury.

Even more progress!

This time Timbou ignored the anklet from the start. After a month we took it off. No injuries. Minimal damage to the anklet.

Success!

Pride cometh before the fall…

Flushed with victory we set off to Congo to test the anklet on another young silverback named Kelle. Kelle had been earlier released into the wild but recaptured when he started ranging near villages where he was in serious danger of being shot. We put the anklet on Kelle with high hopes that it could provide an early warning system. Within four hours he had ripped the antenna out. By the next day he had ripped one third of the belt away. We took it off after 48 hours.

Abject failure!

Back to the drawing board.Where we went wrong was in not recognizing that Timbou had lost two of his canine teeth during childhood rough and tumble play in England. Lacking opposable canines, he could not bite effectively at the belting material. With an immaculate set of canines and the huge bite pressure generated by the massive halo of muscle on his sagittal crest, Kelle made short work of reinforced plastic that a human could not even dent.

This time instead of buying an off-the-shelf product from a commercial telemetry provider we commissioned a local metal shop, Mill Turn Engineering in St Ives UK, to custom build us a Gorilla Proof aluminium housing that we affectionately call IronMan. We also partnered with Microsoft Research in Cambridge, a lead institution on Mataki, a multifunctional radio telemetry system for wildlife conservation applications. We put the Mataki board into Ironman and attached it to a different silverback at Port Lympne using a stainless steel chain. Kush has canines every bit as lovely as Kelle.

After the first day Kush ignored the anklet. After a month we took it off. Ironman did not injure Kush. Kush did not injure IronMan.

Success! Really this time…

Our next step is to make modifications to Mataki that will increase the signal transmission range and save battery life. These should be done by midsummer, at which point we will go back to Africa for some ground truthing then attachment to a reintroduced gorilla. We also have two tourism companies ready to use the anklet for gorilla habituation. But that is another story…

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CONVENTIONAL WISDOM: It’s best for gorillas if they have little to do with humans. CONTRARY VIEW: Tracking great apes for eco-tourism purposes can protect the species.

For years, scientists have attached tracking devices to a variety of animals, but they have mostly steered clear of tagging great apes. In recent years, conservationists have worried that habituating gorillas, specifically, to humans is unwise since we are among the greatest threats to the species’ survival…